Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells

J Inorg Biochem. 2007 Sep;101(9):1265-9. doi: 10.1016/j.jinorgbio.2007.06.004. Epub 2007 Jun 13.


Iron- and aluminum-sulfate together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate- to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism
  • Humans
  • Metals / pharmacology*
  • MicroRNAs / biosynthesis*
  • Reactive Oxygen Species / metabolism*
  • Sulfates / pharmacology*


  • Metals
  • MicroRNAs
  • Reactive Oxygen Species
  • Sulfates